In case the initially scheduled period of an authorized clinical trial needs to be extended, the Sponsor or Contracted Research Organization should request the National Health Institute an extension of the corresponding period 30 days before expiration. This authorization will not exceed 12 months and is granted by means of a Board Resolution issued by the National Health Institute.

Procedure’s duration:

Requirements

Extension Request (Enter the data according to the e-form available in REPEC, by using your assigned user account and password assigned HERE and attach the printed form)

Report explaining the reasons for the extension request. (Enter the data according to the e-form available in REPEC and attach the printed form)

Extension approval issued by the research institution(s) where the clinical trial is conducted

Extension approval issued by the Institutional Research Ethics Committee registered in the National Health Institute which evaluated the clinical trial.

Additional List of Supplies necessary for the execution of the clinical trial (printed and electronic version) as per Annex 10, if required

Procedure’s receipt of payment issued by the National Health Institute’s checkout.

Frequently Asked Questions

When an extension should be requested?The Sponsor or CRO should consider submitting a clinical trial extension request in case the project period has expired.

In case a new research site has to be included in an authorized clinical trial, the Sponsor or Contracted Research Organization should request the National Health Institute a Research Site Expansion.

This authorization is granted by means of a Board Resolution issued by the National Health Institute.

Procedure’s duration:

Requirements

Addition of new research sites request Request (Enter the data according to the e-form available in REPEC, by using your assigned user account and password assigned HERE and attach the printed form).

Authorization issued by the additional research Institutions(s) where the clinical trial will be conducted.

Report explaining the reasons for the research site expansion (Enter the data according to the e-form available in REPEC)

Research protocol and/or Informed Consent Amendment Approval issued by an Institutional Research Ethics Committee registered in the National Health Institute, for the additional research site.

Affidavit,signed by the Sponsor and Principal Investigator Principal about the additional research site Affidavit, out as per Annex 14 of the Procedures Manual (Fitting out in Annex 3 of the Clinical Trials Regulation).

Additional List of Supplies necessary for the execution of the clinical trial (printed and electronic version) as per Annex 10, if required

Short descriptive Curriculum Vitae of the Principal Investigator(s) and Co-investigator(s).

Updated and signed. Indicate prior experience in Research, especially in Clinical Trials, indicating studies titles, protocol code and position performed

Copy of Good Clinical Practices training certificate should be attached for each Investigator (principal and co-investigators)

Procedure’s receipt of payment issued by the National Health Institute’s checkout for each additional research site.

In case an authorized clinical trial needs to extend or modify the list of supplies, the Sponsor or Contracted Research Organization should request the National Health Institute the Extension or Amendment of the List of Supplies

Procedure’s duration:

Requirements

Request for Extension or Amendment of List of Supplies (Enter the data according to the e-form in REPEC, by using your assigned user account and password HERE and attach the printed form).

Report explaining the reasons for the Request for Extension or Amendment of List of Supplies. (Enter the data according to the e-form available in REPEC).

Additional List of Supplies necessary for the execution of the clinical trial (printed and electronic version) as per Annex 10, if required.

When a request for Extension / Amendment of List of Supplies is submitted the provider who will procure the supplies must be defined.

If new supplies are included, Annex 10 should indicate these new products, and those supplies which were previously requested and authorized should not be repeated.

The quantities required in Annex 10 should be explained, considering the trial duration time, number of patients to be enrolled, number of research sites, number of dose per patient, reserve stock, product expiration date, among others.

The parameters considered for the calculation of safety stock or reserve stock should be clearly explained.

If there is a mistake in a request for Extension / Modification of List of Supply by the Sponsor or CRO, a new request should be submitted in order to create a new file

The Closure of a Clinical Trial Research Site should be requested when all the activities of a research site are cancelled in advanced (for any reason upon request of the Sponsor or as a safety measure) (Art. 7, Number 4, Clinical Trials Regulation).

This authorization is granted by means of a Board Resolution issued by the National Health Institute.

Procedure’s duration:

Requirements

Research Site Closure Request (Enter the data according to the e-form in the REPEC, by using your assigned user account and password HERE and attach the printed form).

Report explaining the reasons for the research site(s) closure request, including the data obtained to the date, and the measures that will be adopted with the research subjects.

Important:

If all the activities of a clinical trial in a research site are terminated in advance, besides requesting the Closure of Research Site, the Sponsor should send the research site’s final report. For this purpose, it should provide the information requested in the e-form available in the Peruvian Clinical Trials Registry (REPEC), and submit the printed version of the same in Documentary Procedure Office of National Health Institute.

Frequently Asked Questions

What procedure should be followed if the activities of a clinical trial are terminated in advance in all the authorized research sites and not in a single site? The closure procedure should be followed for each research site?If all the activities of a clinical trial are terminated in advance, a Notification for Early Termination of Clinical Trial should be done

When is it correct to request the closure of a research site?In case all activities in the research site, related to the clinical trial, have finished in accordance with the protocol, the request for the closure of a research site would not apply. Instead, the research site final report should be sent by means of the e-form available in REPEC. With this procedure, the clinical trial status for such research site would be Finished.

For any authorized clinical trial that due to any reason is (temporarily) stopped, the Sponsor or Contracted Research Organization will request the Clinical Trial Suspension to the National Health Institute.

This authorization is given by means of a Board Resolution issued by the National Health Institute

Procedure’s duration:

Requirements

Clinical Trial Suspension Request. (Enter the data according to the e-form in the REPEC, by using your assigned user account and password HERE and attach the printed form).

Report explaining the clinical trial suspension request and including the data obtained until the suspension and the measures adopted for research subjects.

The notification for Clinical Trial Advanced Termination should be sent when all the activities of a research site are cancelled in advanced (for any reason upon request by the Sponsor, by the OGITT or the Research Ethics Committee) (Art. 7, Number 4, Clinical Trials Regulation).

This authorization is given by means of a Board Resolution issued by the National Health Institute.

Procedure’s duration:

Requirements

Notification of Clinical Trial Advanced Termination sent to the General Director of Research and Technological Transfer General Office (OGITT) of National Health Institute.

Report explaining the clinical trial advanced termination and including the data obtained until the suspension and the measures adopted for research subjects.

Important:

If all the activities of a clinical trial in a research site are terminated in advance, the Sponsor should also send the corresponding final reports.

For any authorized clinical trial which original protocol is amended, including change of Clinical Trial’s Title, the Sponsor or Contracted Research Organization should request the authorization of amendment to the National Health Institute. This authorization is given by means of a Board Resolution.

Procedure’s duration:

Requirement

Amendment Request (Enter the data according to the e-form in the REPEC, by using your assigned user account and password HERE and attach the printed form).

Report explaining and detailing the change to the clinical trial title (Enter the data according to the e-form in the REPEC).

Research protocol Amendment Approval by a Research Institutional Ethics Committee registered in the National Health Institute.

Receipt of payment for procedure fees issued by the National Health Institute’s checkout.

For any authorized clinical trial that requires an amendment to the original protocol and/or informed consent forms which do not include Clinical Trial’s Title, The Sponsor or Contracted Research Organization must apply the clinical trial amendment report.

This authorization is granted by means of an Official Letter issued by OGITT

Procedure’s duration:

Requirements

Amendment Report request, including the list of documents to be amended (document, version and date): Enter the data according to the e-form in the REPEC, by using your assigned user account and password HERE and attach the printed form.

Report explaining the amendment proposed for the clinical trial. It should contain:

List of the changes to the protocol / informed consent forms

Rationale of proposed changes.

Protocol and/or informed consent with highlighted changes or with track changes, in Spanish and original language, if different from Spanish.

Protocol and/or consent(s) with amendment included, in Spanish and English.

Approval of Amendment to research protocol and/or Informed Consent issued by the Institutional Research Ethics Committee registered in the National Health Institute.

Important:

The Amendments to Research Protocol proceed only after authorization by OGITT / INS

OGITT will not authorize Amendment modifying the original objectives of Protocol, treatment time and research product(s).

Progress reports will be submitted by the Sponsor or Contracted Research Organizations to National Health Institute (INS) for each authorized Research Site and pursuant to the e-form available in REPEC. This report will be submitted on a quarterly or half yearly basis as from the issuance date of the Clinical Trial Authorization Resolution.

Requirements

Send to INS as per the e-form available in REPEC, by using the user account and password assigned HERE and attach the printed form. This report should be submitted by means of the Documentary Procedure Office of INS

Each Progress Report should be submitted with its corresponding file and by separate.

Important:

The following information must be included in the Clinical Trial Progress Report:

No. of Subjects who failed the screening (screen failure): This number is deduced from the subtraction between screened patients and enrolled patients.

No. of subjects with clinical failure: Those patients who entered to the study and were considered as non-responsive to the prescribed treatment or who worsened their condition.

Serious Adverse Events (SAEs): In addition to the number of SAEs in item 5, a summary table of serious, expected and unexpected adverse events notified to the date should be attached; it is created by REAS-Net System. This table should indicate:- Patient Identification Code, Serious Adverse Event, Occurrence date, date of notification to the National Health Institute, SAE outcome*, relation to the research product. Indicate if the SAE was expected or unexpected.- *SAE’s outcome: Completely recovered, Recovered with sequel. Improved condition, Unchanged and still present condition, Worsened condition, Death.

Quarterly or Half-yearly Report of Deviations/Breaches to the Protocol of every research sites occurred in the indicated term. The following information should be indicated at least: patient’s identification code, date of deviation (dd/mm/yyyy), deviation description, type of deviation (numeric code can be used*), corrective measure taken and its reasons, date of corrective measure enforcement (dd/mm/yyyy), date of notification to the ethics committee (dd/mm/yyyy). This information can be sent in the Sponsor’s format.

Quarterly or Half-yearly Report of the Serious and Unexpected Adverse Reactions related to the research product, occurred abroad. This is a written summary list of the SUSARs reports, occurred in the period indicated, which includes at least the following information: No. of Protocol involved, No. of Notification, date of notification, type of report, country of origin, participant’s code, age, sex, SAE’s description, date of start/end, suspected product (dose, frequency, route), outcome, causality. The Sponsor should submit an evaluation of the research product safety profile and the risk-benefit balance in order to continue the study. The list and each report should be sent in digital format (CD).

*TYPE OF DEVIATIONS

Procedures related to the IC

Inclusion/Exclusion criteria

Study drug/dosage

Evaluations and/or lab procedures required in the study

Study procedures

Serious Adverse events/device adverse effects report

Randomization procedures

Program and/or visit interval

A deviation that affects the efficacy valuation

Concomitant therapy

Others

Frequently Asked Questions

How should a Progress Report be submitted?The Sponsor or CRO should consider the following recommendations when submitting a progress report:a. Submit the progress reports of all the research sites participating in the clinical trial, including even those which may have not enrolled any patient.b. Strictly follow the indications of the Progress Report form, Annex 12 of the Procedures Manual published in the website of National Health Institute.

When should a progress report be submitted?The progress report submission term is indicated in the Board Resolution that authorized the clinical trial execution in the country. Time is counted since the date of issuance of such resolution. Therefore, the progress report submission should be carried out for all the research sites even those extended after the clinical trial authorization.

What is the meaning of each item in the research subject progress report in relation to the research subjects?

Screened Patients: Selected patients who, after signing the Informed Consent, are submitted to a series of analysis and visits to determine if they comply with the inclusion criteria and who not necessarily will be enrolled or randomized.

Enrolled patients: Patients who, after signing the informed consent and gone through analysis and visits, comply with the inclusion criteria and finally enter into the study and are randomized to participate in one of the arms as per the study design.

Withdrawn patients: Patients who are withdrawn by Investigator’s or Sponsor’s decision, or who leave the study by their own decision.

Patients who completed the study: Patients who complete the study drug stage and who also have a final follow up visit.

Patients with clinical failure: Patients who entered the study but were considered as non-responsive to the prescribed treatment or whose condition worsened.

Pending enrolment patients: Number of patients who should be enrolled, in accordance with the assignation for our country before the beginning of the study, pursuant to the number of sites. The Sponsor or CRO should divide the number of patients by country and then by site. For example, if there are 10 sites in Peru, where 100 patients are planned to be enrolled, then each site should include 10 patients, and if at the moment of submitting the progress report of a site, this has only enrolled 6 patients, there would be 4 patients pending for enrolment in such site.

How do I indicate the number of patients with screening failure?This number of patients is deductible from the screened patients minus enrolled patients.

Research Site Final ReportOnce the Clinical Trial is completed, the Sponsor or Contracted Research Organization will immediately send the final report of each research site to OGITT, in a maximum term of thirty (30) calendar days after the Closure Visit conducted by the monitor.RequirementsSend INS as per e-form available in REPEC, using the user account and password assigned HERE and attach the printed form. This report should be submitted by means of the Documentary Procedure Office of INS.Each final report should be submitted in its corresponding file and by separate.

National Final ReportOnce the clinical trial of all research sites nationwide is completed, the Sponsor or Contracted Research Organization will send the National Final Report in a maximum term of sixty (60) calendars days after the final report of the last research siteRequirementsSend INS as per e-form available in REPEC, using the user account and password assigned HERE and attach the printed form. This report should be submitted by means of the Documentary Procedure Office of INS

International Final ReportOnce the Clinical Trial is completed, the Sponsor or Contracted Research Organization will send the International Final Report, in a maximum term of twelve (12) months after the finalization of the clinical trial in all the research sites worldwide.Requirements- Send INS as per e-form available in REPEC, using the user account and password assigned HERE and attach the printed form. This report should be submitted by means of the Documentary Procedure Office of INS- The International Final Report should include the final results and the study conclusions before publication.

Serious Adverse Events and Unexpected Adverse Reactions occurred in the country should be notified to the Research and Technological Transfer General Office (OGITT) of National Health Institute via REAS-NET. To fill the data serious adverse events report in REAS-NET system, follow the Instructions available in the Procedure Manual for the conduction of clinical trials in Peru (Annex 11)

All the Serious Adverse Events (related or not) should be notified to INS by the Sponsor in a maximum term of 7 days as from the occurrence or acknowledgement of the event (Art. 109, paragraph a, from Supreme Decree 017-2006-SA), otherwise it would be considered an infraction (art 131, paragraph f from the Amendment, from Supreme Decree 006-2007-SA) subject to sanction (Chapter II, title XII Art. 132 from Supreme Decree 017-2006-SA).

Requirements

All the serious adverse events (related or not) and unexpected adverse reactions should be sent in a maximum term of seven (07) days, as from the occurrence or acknowledgement of the event (Enter the data according to the e-form available in REAS-NET, using your assigned user account and password and attach the printed form. This report should be submitted by means of the Documentary Procedure Office of INS.

Complete the previous information within the following eight (08) days; otherwise, you should submit update reports. Once you complete the follow up, send the final report via REAS-NET, and after the blind is opened, if appropriate.

Frequent mistakes

What are the most frequent mistakes when filling the Report of Serious Adverse Events in Clinical Trials?

Incomplete or mistaken data about the trial, which makes difficult to identify it: Please, verify the Protocol Code is indicated, as well as the Authorization Resolution and date.

Incomplete information about the SAE: Report the patient code without changes; do not add more numbers or letters; indicate the SAE start date. Provide an accurate description of the SAE; for instance, do not indicate abdominal pain instead of the real cause: hemorrhagic pancreatitis; cardio-respiratory infarction instead of disease progression. In order to uniform terms, the WHO Adverse Reactions Terminology Dictionary or MedDRA should be used. Make a complete summary of the serious adverse event and complete the information with follow up and final reports, if applicable. Report the event outcome and the recovery date or event termination.

Missing information about the research product: Indicate the administered research product(s) and indicate the suspect product (which could be the concomitant drug); likewise, indicate the measures taken in relation with the research product, especially if it was temporarily interrupted or it was definitively terminated and indicate what happens when the research product is interrupted, when the dose is reduced and when it is administered again (re-exposure). Besides, indicate if there was lack of adherence to the treatment or if it was a medication mistake.

Missing information about the measures taken for the research subject: Specify the support therapy or drug therapy in an additional sheet; do not indicate it in the space for concomitant drug.

Missing information about the concomitant drug: Treatment start and termination dates are important as well as comments in case you consider the adverse event is caused by a concomitant drug.

Missing information about auxiliary laboratory tests: They can be provided in a separate sheet, indicating the normal or baseline values and including your comments about the results of the laboratory tests or other diagnosis tests which support the causality.

Prevent Duplicity of reports and contradictions between initial and final report. Likewise, do not fill in the form by hand.

*Each procedure related to Clinical Trials should be submitted in its corresponding file and by separate.

ADDITIONAL CONSIDERATIONS:

All the corresponding items in the Report Form of Serious Adverse Events should be filled with complete information and in chronological order, to make it easier to understand. Use the correct term to indicate the SAE; we recommend checking the terms in the WHO Adverse Reactions Terminology Dictionary (WHO-ART) included in the system.

Serious and unexpected adverse events reports, suspected to be related to the research product (SUSARs), occurred in the country, should be reported as soon as possible, by written in CIOMS form and in digital form (CD)

The Sponsor or CRO will send quarterly or half-yearly a printed summary in Excel of serious and unexpected adverse reactions, occurred in the authorized clinical trial, other clinical trials with the same research product or in a different use context. Likewise, CIOMS reports of international serious and unexpected adverse reactions should be sent in digital form together with the printed Excel version.

The sponsor should send as soon as possible, in CIOMS form, the SUSARs Reports occurred abroad, to the investigator, and through him, it will be sent to the Institutional Research Ethics Committee (CIEI)

Other adverse events described in the Investigator’s Brochure should be notified or reported in accordance with the procedures described in the Procedure Manual for the conduction of Clinical Trials in Peru.

Any expedite safety report, about any event threatening the safety of study participants and/or alters the risk/benefit of the study should be sent separately as soon as possible, in accordance to the Clinical Trials Regulation, Supreme Decree No. 017-2006-SA, Article 107 paragraph d) “...In case of a relevant safety problem, a report will be prepared separately without prejudice of the periodicity mentioned in Chapter II herein, and will be sent to the Health National Institute and to the corresponding Research Ethics Committee in a maximum term of seven working days”.

NOTE: Non Serious Adverse Events related to the research product will be notified to the Research and Technological Transfer General Office (OGITT) of National Health Institute along with the corresponding progress report in digital version.